ORIGINAL RESEARCH
published: 24 April 2019
Edited by:
Hans Van Rostenberghe,
University of Science, Malaysia
Reviewed by:
Antonio Arbo,
Independent Researcher, Asuncion,
Paraguay
Arturo Solis-Moya,
Dr. Carlos Sáenz Herrera National
Children’s Hospital, Costa Rica
*Correspondence:
Elisabetta Pandolfi
pandolfi.elisabetta@gmail.com
Specialty section:
This article was submitted to
Pediatric Infectious Diseases,
a section of the journal
Frontiers in Pediatrics
Received: 21 September 2018
Accepted: 01 April 2019
Published: 24 April 2019
Citation:
Pandolfi E, Gesualdo F, Rizzo C,
Carloni E, Villani A, Concato C,
Linardos G, Russo L, Ferretti B,
Campagna I and Tozzi A (2019)
Breastfeeding and Respiratory
Infections in the First 6 Months of Life:
A Case Control Study.
Front. Pediatr. 7:152.
doi: 10.3389/fped.2019.00152
Frontiers in Pediatrics | www.frontiersin.org
doi: 10.3389/fped.2019.00152
Breastfeeding and Respiratory
Infections in the First 6 Months of
Life: A Case Control Study
Elisabetta Pandolfi 1*, Francesco Gesualdo 1 , Caterina Rizzo 1 , Emanuela Carloni 1 ,
Alberto Villani 2 , Carlo Concato 3 , Giulia Linardos 1 , Luisa Russo 1 , Beatrice Ferretti 1 ,
Ilaria Campagna 1 and Alberto Tozzi 1
1
Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy,
2
Department of Pediatrics, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy, 3 Virology Unit, Laboratory Department,
Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
Background: Viral respiratory tract infections (VRI) are a major reason for hospitalization
in children younger than 5 years. A case control study was conducted to investigate the
potential role of breastfeeding in protecting children <1 year of age from VRI.
Methods: Patients admitted for a respiratory tract infections routinely underwent
a nasopharyngeal aspirate, which was tested with an RT-PCR for 14 respiratory
viruses. Hospitalized infants positive for viruses were enrolled as cases; healthy controls
were enrolled among patients admitted for ultrasound hip screening. The effect of
breastfeeding on pertussis was investigated through multivariable analysis.
Results: We enrolled a total of 496 patients: 238 cases and 258 healthy controls.
Among cases, eighty-six patients (36.1%) had a rinovirus, 78 (32.8%) an RSV, 22 (9.2%)
an adenovirus, and 37 (15.5%) a coinfections with multiple viruses. The number of
households was significantly higher in cases (mean in cases 4.5; mean 3.7 in controls, p
< 0.001) and the proportion of infants having siblings (79% in cases vs. 43% in controls,
p < 0.001). Proportion of smoking mothers was higher in cases than in controls (21.4 vs.
10.1%, p = 0.001). Among cases 44.5% were exclusively breastfed at symptoms onset
vs. 48.8% of healthy controls. According to the multivariable analysis, being exclusively
breastfed at symptom onset was associated with a higher risk of viral respiratory infection
(3.7; 95% CI 1.64–8.41), however a longer breastfeeding duration was protective (OR
0.98; 95% CI 0.97–0.99). Also having at least one sibling was associated to a higher
risk (OR 3.6; 95% CI 2.14–5.92) as well as having a smoking mother (OR 2.6; 95%
CI 1.33–4.89).
Conclusions: Breastfeeding remains a mainstay of prevention for numerous diseases
and its protective role increases with duration. However, being breastfed when mothers
carry a respiratory infection may increase the risk of transmission, acting as a proxy for
closer contacts. In future studies, potential confounding variables as pattern of contacts
with other individuals, should be taken into account.
Keywords: respiratory infection, breastfeeding, prevention, viral infection, pediatrics, breast milk
1 April 2019 | Volume 7 | Article 152
Pandolfi et al.
BACKGROUND
Respiratory tract infections are a leading cause of morbidity in
children.
Studies conducted in industrialized countries report a
prevalence of respiratory tract infections ranging from 3.4 to
32.1% in the first year of life (1–4). Respiratory tract infections
are also a major reason for hospitalization in children younger
than 5 years (5–7).
Different studies have explored and confirmed the role of
clinical and socioeconomic risk factors for respiratory tract
infections, including birth weight, gestational age, socioeconomic
status, ethnicity, number of siblings, day care attendance,
and parental smoking (4, 8, 9). Breastfeeding is included
among the protective factors for respiratory infections in
infants. The protective role of breastfeeding against respiratory
infections has been repeatedly demonstrated for children living
in developing countries (10–12). Although breastfeeding is
described as protective also in industrialized countries, different
study designs, definitions (e.g., for infant feeding and kind
of infection), timing of evaluation of exposure (feeding), and
outcome (infection), have been used in studies performed
this setting.
Most studies confirm a protective role of breastfeeding against
respiratory infections in the long term, as the outcomes are often
measured after 6 months of age, or even at 1, 2, or 6 years (13),
showing a persistent protective effect even after breastfeeding has
been stopped.
In fact, protection seems to be time dependent: in a large
cohort of infants in the UK, those who were breastfed for
<4 months had a higher risk of hospitalization for infectious
diseases in the first year of life compared with those who were
breastfed for more than 4 months (14). In addition, infants who
were breastfed for 4–6 months showed a higher risk of both
pneumonia and recurrent otitis media compared to those who
were breastfed for 6 months or longer (15–17).
Fewer are the studies analyzing the protective role of
breastfeeding in the first 3 months of life. While Duijts et al.
report a protective effect of breastfeeding in children exclusively
breastfed until 4 months of age compared to never breastfed
infants (1) other studies report a weaker protection for children
younger than 3 months (18) or no protection at all (19).
We report here the results of a case-control study exploring
the association of breastfeeding with viral respiratory infections
in a metropolitan area, in children younger than 12 months
of age.
METHODS
Study Design and Setting
We conducted a case-control study in one large metropolitan
pediatric hospitals, located in Rome, Italy, between June 2012 and
February 2018. Bambino Gesù Children’s Hospital is the largest
pediatric research hospital in Europe. It accounts for nearly 600
beds and admits several patients from outside the Lazio Region,
especially those with chronic and severe diseases. It performs
Frontiers in Pediatrics | www.frontiersin.org
Breastfeeding’s in Respiratory Infections
every year a total of over 1 million and 690 thousand pediatric
clinical encounters.
The study was supported by the ECDC (European Center
for Disease Control) within the Pertinent project (Pertussis in
Infants European Network), a European hospital-based network
dedicated to measuring pertussis burden in infants and to
studying pertussis vaccine effectiveness.
The objective of the present study was to analyze the role of
breastfeeding as a protective factor for viral respiratory infections
in children younger than 6 months of age. Data on the effect of
breastfeeding on pertussis were reported in a recently published
paper (20).
Patients admitted for a respiratory tract infection routinely
underwent a nasopharyngeal aspirate, which was tested with a
real time polymerase chain reaction (RT-PCR) for 14 respiratory
viruses (listed in the next paragraph).
Patients < 6 months of age with a positive RT-PCR for one of
these viruses were enrolled as cases.
A group of healthy controls aged < 6 months were
systematically enrolled among healthy infants admitted as
outpatients in the same hospital for hip ultrasound screening,
on Tuesdays and Thursdays, in the same period during which
cases were recruited. Infants with a previous hospitalization
were excluded.
Nasopharyngeal Aspirate Collection and
RT-PCR for Viruses
Nasopharyngeal aspirates were performed and processed using
a specific panel detecting the following viruses: RSV, influenza
virus A and B, human coronavirus OC43, 229E, NL-63,
and HUK1, adenovirus, hRV, parainfluenza virus 1–3, human
metapneumovirus-hMPV, and human bocavirus-hBoV.
Samples of nasopharyngeal aspirate were collected within 24 h
from hospital admission and processed immediately, or stored at
−70◦ C until performing the test.
Nucleic acids were extracted from a 200 µl sample of
nasopharyngeal aspirates and purified, using the EZ1 Virus Mini
Kit v. 2.0 on the EZ1 Advanced XL platform (Qiagen, GmbH,
Hilden, Germany). Nucleic acid extracts were eluted into 90 µl of
buffer and processed immediately.
Data Collection
For each enrolled patient (cases and controls), the following
data were recorded: socio demographic data, gestational age,
kind of delivery, birth weight, parents’ level of education and
employment, kind of feeding at symptom onset (exclusive
breastfeeding, partial breastfeeding, artificial feeding), number of
households, number of smokers in the family.
Data were collected through a questionnaire administered
to parents of patients at enrolment, after signing an
informed consent.
Epidemiological data were recorded in an electronic database
(Microsoft Access).
Statistical Analysis
In Italy, the prevalence of exclusive breastfeeding at 3 months has
been estimated to be nearly 60% (21). Considering this estimate,
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Pandolfi et al. Breastfeeding’s in Respiratory Infections

we calculated that a sample of 490 patients was sufficient to show TABLE 1 | Socio-demographic characteristics of patients enrolled.
an odds ratio of 0.6 for exclusively breastfed infants vs. infants
Respiratory Healthy Total p-value
with partial breastfeeding or artificial feeding, with a power of 80 infections (controls) (N = 496)
and a 95% confidence level. (cases) (N = 258)
Proportions were compared using the Chi-square test or (N = 238)
the Fisher exact test. Differences between means were studied
through the Student’s T-test. A P-value < 0.05 was considered Male (n, %) 112 (47.1) 129 (50.0) 241 (48.6) 0.513

statistically significant. Age in months 2.0 (1.1) 2.4 (0.8) 2.2 (1.0) < 0.001
(mean, sd)
As the aim of our study was to analyse the effect of
Caucasian (n, %) 216 (90.8) 240 (93.0) 456 (91.9) 0.354
exclusive breastfeeding on the risk of respiratory infections,
Gestational age, 37.7 (2.6) 38.9 (1.9) 38.4 (2.3) < 0.001
we decided to include in the same group artificial feeding
weeks (mean, sd)
+ partial breastfeeding at symptom onset or at enrolment.
Premature birth 50 (21.0) 18 (7.0) 68 (13.7) < 0.001
A multivariable logistic regression analysis was performed in (n, %)
order to study the effect of exclusive breastfeeding (exclusive vs. Birth weight in kg 3.0 (0.6) 3.2 (0.5) 3.11 (0.58) < 0.001
partial breastfeeding or artificial feeding, at symptom onset for (mean, sd)
cases, or at enrolment for controls) and its duration (days) on Caesarean birth 117 (49.2) 107 (41.5) 224 (45.2) 0.086
the occurrence of respiratory tract infections, adjusted for the (n, %)
following variables: age (days), sex (male vs. female), ethnicity Employed mother 138 (58.0) 158 (61.2) 296 (59.7) 0.460
(caucasian vs. non caucasian), gestational age at birth (weeks), (n, %)
birth weight (kg), kind of delivery (vaginal vs. cesarean), parents’ Employed father 221 (92.9) 238 (93.0) 459 (92.9) 0.961
employment, parents’ level of education (university degree vs. (n, %)

lower), parents’ smoking habits, number of households, having Mother with university 68 (28.6) 102 (39.5) 170 (34.3) 0.010
degree (n, %)
at least 1 sibling.
Father with university 52 (21.9) 80 (31.4) 132 (26.8) 0.017
Multicollinearity between the independent variables was degree (n, %)
assessed by studying the correlation matrix and examining the
Households 4.5 (1.8) 3.7 (0.9) 4.1 (1.5) < 0.001
tolerance and the variance inflation factor (VIF). (mean, sd)
Stata 13 was used for statistical analysis. One or more brothers 188 (79.0) 111 (43.0) 299 (60.3) < 0.001
(n, %)

ETHICAL APPROVAL Smoker mother 50 (21.4) 26 (10.1) 76 (15.5) 0.001

(n, %)
The study was approved by the Bambino Gesù Children’s Smoker father (n, %) 80 (34.2) 83 (32.2) 163 (33.1) 0.635
Hospital Ethical Committee (protocol RF-2010-2317709).

RESULTS a respiratory syncytial virus, 22 (9.2%) adenovirus, and

Population
Socio-demographic characteristics of the study population are
shown in Table 1. We enrolled a total of 496 patients: 238
cases and 258 healthy controls. Healthy controls were older
than cases (mean age of controls 2.38 months, mean age of
cases 1.99 months, p < 0.001). The proportion of premature
babies was significantly higher in cases than in controls (21 vs.
7%, p < 0.001). The proportion of mothers and fathers with
a university degree was higher in controls (for mothers 39.5
vs. 28.6% respectively, p = 0.010; for fathers, 31.4 vs. 21.9%
respectively, p = 0.017). The number of households was higher
in cases (mean 4.5) than in controls (mean 3.7, p < 0.001),
and so was the proportion of infants having siblings (79% in
cases vs. 43% in controls, p < 0.001). Proportion of smoking
mothers was higher in cases than controls (21.4 vs. 10.1%,
p = 0.001).
Among children with an acute respiratory tract infection,
19.3% of mothers had respiratory symptoms.
Viral Characteristics
Of 238 patients with respiratory infections, eighty-six
patients (36.1%) had a rhinovirus infection, 78 (32.8%)
37 (15.5%) had coinfections with multiple viruses, such
as Coronavirus, Metapneumovirus, Influenza A and B,
Parainfluenza virus.
The median duration of hospital admission was 6 days with
no differences by type of virus. Among those with respiratory
infections, a total of 74 patients (31.1%) had complications
during hospital admission, and nearly a half of these (49.4%) had
a RSV infection.
Breastfeeding
Table 2 describes the kind of infant feeding at symptom onset.
A proportion of 46.8% of enrolled patients were exclusively
breastfed at enrollment. Among patients with respiratory tract
infections, 44.5% were exclusively breastfed at symptoms onset
(Table 2) while 48.8% of patients were exclusively breastfed
at enrolment among healthy controls. The mean duration of
exclusive breastfeeding was 35.8 days in cases and 41.6 days
in controls.
Among cases, 19% of children had a mother with respiratory
symptoms while breastfeeding. No differences were observed
in breastfeeding duration between cases having a mother with
symptoms and those without.

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Pandolfi et al. Breastfeeding’s in Respiratory Infections

TABLE 2 | Kind of breastfeeding at symptoms onset in the study population. TABLE 3 | Factors associated to the risk of having an acute viral respiratory
infection according to a logistic regression model.
Respiratory Healthy Total p
infections (N = 258) (N = 496) OR 95%CI p
(N = 238)
Age (days) 0.99 0.98–1.00 0.043
Patients with exclusive 106 (44.5) 126 (48.8) 232 (46.8) 0.626 Male 0.85 0.55–1.30 0.456
breastfeeding at
Caucasian 0.77 0.35–1.73 0.534
symptom onset (n, %)
Gestational age, weeks 0.84 0.73–0.96 0.012
Days of exclusive 35.8 (42.97) 41.6 (36.97) 38.8 (40.02) 0.110
breastfeeding prior to Birth weight, grams 0.71 0.43–1.17 0.174
enrollment (mean, sd) Vaginal birth 1.30 0.83–2.04 0.250
Never breastfed (n, %) 85 (35.7) 72 (27.9) 157 (31.7) 0.062 Mother with university degree 0.69 0.40–1.20 0.190
Father with university degree 0.67 0.39–1.17 0.160
Employed mother 1.12 0.69–1.80 0.654
Employed father 1.32 0.56–3.15 0.527
In addition, we found that nearly 80% of household contacts Exclusive breastfeeding 3.7 1.64–8.41 0.002
of cases had respiratory symptoms at their enrollment. Breastfeeding duration, days 0.98 0.97–0.99 0.001
The mean length of hospital stay was 7.6 days in children Number of households 1.16 0.93–1.44 0.189
exclusively breastfed compared to 12.5 days in those with partial One or more siblings 3.56 2.14–5.92 <0.001
breastfeeding or artificial feeding, but this difference was not
Smoking mother 2.55 1.33–4.89 0.005
statistically significant.
Smoking father 0.76 0.47–1.23 0.264
Among cases, mothers with a university degree were
32.1% among those who were exclusively breastfeeding at
symptom onset and 25.8% among those providing partial
breastfeeding or artificial feeding. As for controls, mothers The association of maternal smoking and respiratory
with a university degree were 47.6% among those who were conditions seems to be linked to the interference of nicotine on
exclusively breastfeeding at symptom onset and 31.8% among lung development (36).
those providing partial breastfeeding or artificial feeding. Regarding breastfeeding, our results confirm the time-
dependent effect of exclusive breastfeeding in the protection
Multivariable Analysis against VRI, which is actually in line with the majority of
According to the multivariable analysis, having at least one published studies (1, 18, 25). Nevertheless, at the same time,
sibling was associated to a higher risk of viral respiratory the multivariable analysis identified exclusive breastfeeding
infection (OR 3.6; 95% CI 2.14–5.92) as well as having as a risk factor for VRI. Some of the previously published
a smoking mother (OR 2.6; 95% CI 1.33–4.89). Being literature are in line with this result. Some authors showed that
exclusively breastfed at symptom onset was associated with a breastfeeding does not provide substantial protection against
higher risk of viral respiratory infection (3.7; 95% CI 1.64– common infectious illnesses during the first year of life (24).
8.41) but protection increased with breastfeeding duration Other studies concluded that a shorter period of breastfeeding
(OR 0.98; 95% CI 0.97–0.99) (Table 3). might increase the risks of illness and physician visits for
lower respiratory tract infections (29). Some authors reported
DISCUSSION that breastfed babies do not have fewer respiratory viral
infections or illnesses, although they may experience less severe
Breastfeeding is a mainstay for the prevention of infectious disease (28).
diseases. The protective effect of prolonged breastfeeding against Evidence on the protective role of breastfeeding against
infectious diseases in children living in developing countries infections of the gastrointestinal tract is more robust (37)
has been well documented (22, 23). However, protection compared to findings on the protection from respiratory
from respiratory infections through breastfeeding in developed infections. This has an immunological explanation. Breastmilk
countries has not been uniformly demonstrated, with major actually contains numerous protective factors such as
differences between methods in most studies (11, 12, 24–28). immunoglobulins, lactoferrin, and lymphocytes, as well as
With the present study, we confirm risk factors previously other factors that may contribute to reduce infant mortality in
identified for respiratory infections in infants: low gestational age, developed countries (25). As a matter of fact, immunoglobulins
young age, having one or more siblings (29, 30). ingested through breastfeeding confer a direct, timely protection
Moreover, in our study, we confirm an association between against microorganisms localized in the gastrointestinal tract,
maternal smoking and the risk of having a viral respiratory which are directly bound by ingested breast milk IgA. On the
infection (OR 2.55; 95% CI 1.33–4.89). As other authors reported, other hand, in order to protect from infections localized in
children of smoking mothers have an increased risk of severe other body sites, ingested immunoglobulins should be absorbed
RSV infection, morbidity, mortality and hospitalizations for through the intestinal mucosa and move to other areas through
respiratory infection and other infectious diseases (31), SIDS the bloodstream. Nevertheless, evidence shows that the process
(32), wheezing and asthma (33–35). of intestinal IgA absorption is not effective (37, 38).

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Pandolfi et al.
One of the factors that should be taken into account when
evaluating the transmission of an infective agent is the pattern
of contacts among individuals, which has been shown to affect
the risk of viral infections in other studies (39, 40).
We recently published a study exploring the pattern of
contacts within the households of infants younger than 6 months,
through the use of Radio-Frequency Identification devices (41).
We showed that families in which the baby is exclusively
breastfed tend to have a more intense contact pattern compared
to families in which the infant receives artificial of mixed
feeding—not only the contacts of the infant with the mother are
more frequent and of a longer duration, but also the contacts
of the infant with the father. In other words, breastfeeding may
represent a proxy for closer contacts of the infant with the
mother and, possibly, with other household members. As contact
patterns vary in different country settings (42), also the influence
of breastfeeding on contact patterns may vary depending on
geographic contexts.
In our study, among cases, nearly 80% of all household
members had respiratory symptoms at enrollment and 19% of
mothers had acute respiratory symptoms while breastfeeding,
suggesting the possible association between mother’s/household
members’ proximity and risk of infection. The increased risk
due to increased proximity is higher in the first months of
life, and is probably counterbalanced in older infants by the
development of the immune system and by other long-term,
immune-modulating effects of breast milk that still need to
be elucidated.
This study has several potential limitations.
The first limitation concerns the study design: we could
not determine parents’ symptoms among controls and we were
not able to measure the pattern of contacts within household
members. A cohort study taking into account contact patterns
in the households would be appropriate to confirm these
observations, although the execution of a study with such
characteristics would entail a complex organization and require
high investments. Moreover, cases were younger than controls,
but this potential confounding effect was adjusted through the
multivariable analysis.
Finally, as our aim was to assess the effect of exclusive
breastfeeding on the risk of respiratory infections, we decided
to include children with partial breastfeeding and those with
artificial feeding in the same subgroup. This is a typical issue
in the design of studies on breastfeeding and health outcomes
and might have biased in the resulting effect of breastfeeding
on respiratory infections. Nevertheless, our retrospective study
design did not allow to assess the specific dose of breastmilk
received by the enrolled infants.
CONCLUSION
Overall, we strongly support the choice of exclusive breastfeeding
as the best possible kind of feeding for infants in the first months
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Breastfeeding’s in Respiratory Infections
of life. Our results support the evidence that breastfeeding effect
toward protection against VRI is dose dependent: the longer the
duration of exclusive breastfeeding, the stronger the protection.
In addition to, we suggest that, in future studies aimed at
assessing the breastfeeding protective role for airborne diseases,
potential confounding variables as pattern of contacts with other
individuals, together with contact symptoms, have to be taken
into account, to avoid bias in interpretation.
Moreover, taking into account the potentially higher
probability of infection transmission in families with frequent
and long contacts among household members, we support the
adoption of recommendations issued by the Center for Disease
Control and Prevention for the prevention of VRI transmission
to infants. According to these recommendations, symptomatic
mothers should thoroughly wash their hands with soap and
water before touching the infant and cover their nose and mouth
with a tissue when sneezing or coughing in close contact with
the infant (43).
Exclusive breastfeeding should be promoted for the first
six months of life, as WHO and CDC strongly recommend,
because the risk of infant morbidity for viral acute respiratory
infections is negatively associated with the duration
of breastfeeding.
ETHICS STATEMENT
This study was carried out in accordance with the
recommendations of name of guidelines, name of committee
with written informed consent from all subjects. All subjects gave
written informed consent in accordance with the Declaration
of Helsinki. The protocol was approved by the Bambino Gsù
ethical committee.
AUTHOR CONTRIBUTIONS
All the authors have contributed significantly to the study,
and have seen and approved the present correspondence. EP
contributed to the conceptualization of the study, wrote, and
reviewed the entire manuscript. FG contributed in writing the
manuscript and to the oversight of the final revision. CR reviewed
the manuscript and contributed to methodology section. EC
provided the statistical analysis of the data and contributed to
data curation. AV contributed to the revision of the manuscript.
CC and GL provided microbiological data and contributed to
write the results sections. LR, BF, and IC contributed to study
design and revised the entire manuscript. AT contributed to
the conceptualization of the study, wrote, and reviewed the
entire manuscript.
FUNDING
The present study was supported by grant from European Center
for Disease Control (ECDC).
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REFERENCES
1. Duijts L, Jaddoe VWV, Hofman A, Moll HA. Prolonged and exclusive
breastfeeding reduces the risk of infectious diseases in infancy. Pediatrics.
(2010) 126:e18–25. doi: 10.1542/peds.2008-3256
2. Wright AL, Taussig LM, Ray CG, Harrison HR, Holberg CJ. The tucson
children’s respiratory study. II Lower respiratory tract illness in the first year
of life. Am J Epidemiol. (1989) 129:1232–46.
3. Neuspiel DR, Rush D, Butler NR, Golding J, Bijur PE, Kurzon M. Parental
smoking and post-infancy wheezing in children: a prospective cohort study.
Am J Public Health. (1989) 79:168–71. doi: 10.1016/j.prrv.2016.08.005
4. Quigley MA, Kelly YJ, Sacker A. Breastfeeding and hospitalization for
diarrheal and respiratory infection in the United Kingdom Millennium
Cohort Study. Pediatrics. (2007) 119:e837–42. doi: 10.1542/peds.2006-2256
5. Williams BG, Gouws E, Boschi-Pinto C, Bryce J, Dye C. Estimates of world-
wide distribution of child deaths from acute respiratory infections. Lancet
Infect Dis. (2002) 2:25–32. doi: 10.1016/S1473-3099(01)00170-0
6. Morikawa S, Hiroi S, Kase T. Detection of respiratory viruses in
gargle specimens of healthy children. J Clin Virol. (2015) 64:59–63.
doi: 10.1016/j.jcv.2015.01.006
7. Leowski J. Mortality from acute respiratory infections in children under 5
years of age: global estimates. World Health Stat Q Rapport Trimestriel De
Statistiques Sanitaires Mondiales. (1986) 39:138–44.
8. Koopman LP, Smit HA, Heijnen ML, Wijga A, van Strien RT, Kerkhof
M, et al. Respiratory infections in infants: interaction of parental allergy,
childcare, and siblings–The PIAMA study. Pediatrics. (2001) 108:943–8.
doi: 10.1542/peds.108.4.943
9. Baker D, Taylor H, Henderson J. Inequality in infant morbidity: causes and
consequences in England in the 1990s. J Epidemiol Commun. Health. (1998)
52:451–8.
10. Bhutta ZA, Ahmed T, Black RE, Cousens S, Dewey K, Giugliani E, et al. What
works? Interventions for maternal and child undernutrition and survival.
Lancet. (2008) 371:417–40. doi: 10.1016/S0140-6736(07)61693-6
11. Hanieh S, Ha TT, Simpson JA, Thuy TT, Khuong NC, Thoang DD,
et al. Exclusive breastfeeding in early infancy reduces the risk of
inpatient admission for diarrhea and suspected pneumonia in rural
Vietnam: a prospective cohort study. BMC Public Health. (2015) 15:9.
doi: 10.1186/s12889-015-2431-9
12. Ajetunmobi OM, Whyte B, Chalmers J, Tappin DM, Wolfson L, Fleming
M, et al. Breastfeeding is associated with reduced childhood hospitalization:
evidence from a Scottish birth cohort (1997-2009). J Pediatrics. (2015)
166:620–625.e4. doi: 10.1016/j.jpeds.2014.11.013
13. Dixon D-L. The role of human milk immunomodulators in protecting against
viral bronchiolitis and development of chronic wheezing illness. Children.
(2015) 2:289–304. doi: 10.3390/children2030289
14. Quigley MA, Carson C, Sacker A, Kelly Y. Exclusive breastfeeding
duration and infant infection. Eur J Clin Nutr. (2016) 70:1420–7.
doi: 10.1038/ejcn.2016.135
15. Lamberti LM, Zakarija-Grković I, Fischer Walker CL, Theodoratou E,
Nair H, Campbell H, et al. Breastfeeding for reducing the risk of
pneumonia morbidity and mortality in children under two: a systematic
literature review and meta-analysis. BMC Public Health. (2013) 13:S18.
doi: 10.1186/1471-2458-13-S3-S18
16. Paricio Talayero JM, Lizán-García M, Otero Puime A, Benlloch Muncharaz
MJ, Beseler Soto B, Sánchez-Palomares M, et al. Full breastfeeding and
hospitalization as a result of infections in the first year of life. Pediatrics. (2006)
118:e92–99. doi: 10.1542/peds.2005-1629
17. Chantry CJ. Full breastfeeding duration and associated decrease in
respiratory tract infection in US Children. Pediatrics. (2006) 117:425–32.
doi: 10.1542/peds.2004-2283
18. Tromp I, Kiefte-de Jong J, Raat H, Jaddoe V, Franco O, Hofman
A, et al. Breastfeeding and the risk of respiratory tract infections
after infancy: the Generation R Study. PLoS ONE. (2017) 12:e0172763.
doi: 10.1371/journal.pone.0172763
19. Yamakawa M, Yorifuji T, Kato T, Inoue S, Tokinobu A, Tsuda T, et al. Long-
term effects of breastfeeding on children’s hospitalization for respiratory tract
infections and diarrhea in early childhood in Japan. Maternal Child Health J.
(2015) 19:1956–65. doi: 10.1007/s10995-015-1703-4
Frontiers in Pediatrics | www.frontiersin.org
Breastfeeding’s in Respiratory Infections
20. Pandolfi E, Gesualdo F, Carloni E, Villani A, Midulla F, Carsetti R., et al.
Does breastfeeding protect young infants from pertussis? Case-control Study
and Immunologic Evaluation. Pediatric Infect Dis J. (2017). 36:e48–e53.
doi: 10.1097/INF.0000000000001418
21. Lauria L, Spinelli A, Grandolfo M. Prevalence of breastfeeding in Italy: a
population based follow-up study. Annali Dell’Istituto Superiore Di Sanita.
(2016) 52:457–61. doi: 10.4415/ANN_16_03_18
22. Chandra RK. Prospective studies of the effect of breast feeding on incidence
of infection and allergy. Acta Paediatr Scand. (1979) 68:691–4.
23. Jason JM, Nieburg P, Marks JS. Mortality and infectious disease
associated with infant-feeding practices in developing countries. Pediatrics.
(1984) 74:702–27.
24. Rubin DH, Leventhal JM, Krasilnikoff PA. Relationship Between
Infant Feeding and Infectious Illness: A Prospective Study of Infants
During the First Year of Life. Pediatrics. (1990) 85:464–71.
25. Kovar MG, Serdula MK, Marks JS, Fraser DW. Review of the epidemiologic
evidence for an association between infant feeding and infant health.
Pediatrics. (1984) 74:615–38.
26. Downham MA, Scott R, Sims DG, Webb JK, Gardner PS. Breast-
feeding protects against respiratory syncytial virus infections. Br Med J.
(1976) 2:274–6.
27. Cushing AH, Samet JM, Lambert WE, Skipper BJ, Hunt WC, Young SA, et al.
Breastfeeding reduces risk of respiratory illness in infants. Am J Epidemiol.
(1998) 147:863–70. doi: 10.1093/oxfordjournals.aje.a009540
28. Frank AL, Taber LH, Glezen WP, Kasel GL, Wells CR, Paredes A. Breast-
feeding and respiratory virus infection. Pediatrics. (1982) 70:239–45.
29. Pettigrew MM, Khodaee M, Gillespie B, Schwartz K, Bobo JK, Foxman
B. Duration of breastfeeding, daycare, and physician visits among
infants 6 months and younger. Ann Epidemiol. (2003) 13:431–5.
doi: 10.1016/S1047-2797(02)00463-5
30. López-Alarcón M, Villalpando S, Fajardo A. Breast-feeding lowers the
frequency and duration of acute respiratory infection and diarrhea in infants
under six months of age. J Nutr. (1997) 127:436–43. doi: 10.1093/jn/127.3.436
31. Metzger MJ, Halperin AC, Manhart LE, Hawes SE. Association of
maternal smoking during pregnancy with infant hospitalization and
mortality due to infectious diseases. Pediatr Infect Dis J. (2013) 32:e1–7.
doi: 10.1097/INF.0b013e3182704bb5
32. Anderson ME, Johnson DC, Batal HA. Sudden Infant Death Syndrome and
prenatal maternal smoking: rising attributed risk in the back to sleep era. BMC
Med. (2005) 3:4. doi: 10.1186/1741-7015-3-4
33. Di Franza JR, Masaquel A, Barrett AM, Colosia AD, Mahadevia PJ. Systematic
literature review assessing tobacco smoke exposure as a risk factor for
serious respiratory syncytial virus disease among infants and young children.
BMC Pediatr. (2012) 12:81. doi: 10.1186/1471-2431-12-81
34. Ko TJ, Tsai LY, Chu LC, Yeh SJ, Leung C, Chen CY, et al. Parental smoking
during pregnancy and its association with low birth weight, small for
gestational age, and preterm birth offspring: a birth cohort study. Pediatr
Neonatol.(2014) 55:20–7. doi: 10.1016/j.pedneo.2013.05.005
35. Behrooz L, Balekian DS, Faridi MK, Espinola JA, Townley LP, Camargo
CA Jr. Prenatal and postnatal tobacco smoke exposure and risk of
severe bronchiolitis during infancy. Respir Med. (2018) 140:21–6.
doi: 10.1016/j.rmed.2018.05.013
36. McEvoy CT, Spindel ER. Pulmonary effects of maternal smoking on the fetus
and child: effects on lung development, respiratory morbidities, and life long
lung health. Paediatr Respir Rev. (2017) 21:27–33.
37. Plenge-Bönig A, Soto-Ramírez N, Karmaus W, Petersen G, Davis S,
Forster J. Breastfeeding protects against acute gastroenteritis due to
rotavirus in infants. European Journal of Pediatrics. (2010) 169:1471–6.
doi: 10.1007/s00431-010-1245-0
38. Carlsson B, Hanson LA. Immunologic effects of breast-feeding on the infant.
In: Ogra P, Lamm ME, Strober W, McGhee JR, Bienestock J, editors. Handbook
of Mucosal Immunology. London: Academic Press (1994).
39. Munywoki PK, Koech DC, Agoti CN, Lewa C, Cane PA, Medley GF,
et al. The source of respiratory syncytial virus infection in infants: a
household cohort study in rural Kenya. J Infect Dis. (2014) 209:1685–92.
doi: 10.1093/infdis/jit828
40. Hall CB, Geiman JM, Biggar R, Kotok DI, Hogan PM, Douglas
GR. Respiratory syncytial virus infections within families.
6 April 2019 | Volume 7 | Article 152
Pandolfi et al.
N Engl J Med. (1976) 294:414–9. doi: 10.1056/NEJM19760
2192940803
41. Ozella L, Gesualdo F, Tizzoni M, Rizzo C, Pandolfi E, Campagna I,
et al. Close encounters between infants and household members measured
through wearable proximity sensors. PLoS ONE. (2018) 13:e0198733.
doi: 10.1371/journal.pone.0198733
42. Mossong J, Hens N, Jit M, Beutels P, Auranen K, Mikolajczyk R,
et al. Social contacts and mixing patterns relevant to the spread
of infectious diseases. PLoS Med. (2008) 5:e74. doi: 10.1371/journal.
pmed.0050074
43. Center for Disease Control and Prevention. Protecting Against Influenza
(Flu): Advice for Caregivers of Young Children. (2018). Available
online at: https://www.cdc.gov/flu/protect/infantcare.htm (accessed
September 7, 2018)
Frontiers in Pediatrics | www.frontiersin.org
Breastfeeding’s in Respiratory Infections
Conflict of Interest Statement: AT has received research grants for vaccine
studies from Sanofi Pasteur MSD, Pfizer and Glaxo SmithKline.
The remaining authors declare that the research was conducted in the absence of
any commercial or financial relationships that could be construed as a potential
conflict of interest.
Copyright © 2019 Pandolfi, Gesualdo, Rizzo, Carloni, Villani, Concato, Linardos,
Russo, Ferretti, Campagna and Tozzi. This is an open-access article distributed
under the terms of the Creative Commons Attribution License (CC BY). The use,
distribution or reproduction in other forums is permitted, provided the original
author(s) and the copyright owner(s) are credited and that the original publication
in this journal is cited, in accordance with accepted academic practice. No use,
distribution or reproduction is permitted which does not comply with these terms.
7 April 2019 | Volume 7 | Article 152